Clinical applications of two-dimensional electrophoresis.

High-resolution two-dimensional electrophoresis has been used in our institute to study sera from patients with multiple myelomas; cerebrospinal fluid from patients with different neurological disorders; blister fluid, dermis, and epidermis from patients with skin diseases; and biopsies from brain tumors; and to search for tumor-associated proteins in cancer biopsies and pre-cancer sera. The method differentiates between all main types of immunoglobulins and gives rise to protein patterns for cerebrospinal fluid that may carry diagnostic information. The pattern of proteins in serum and blister fluid is almost identical, confirming that the latter is a filtrate of serum. We also analyzed sera collected from patients several years before it was clinically recognized that they had cancer (JANUS serum bank), in an attempt to find tumor-associated proteins in serum at an early stage of the disease. We encountered difficulties in detecting trace proteins, due to masking effects of such major serum-protein constituents as albumin. A combination of computerized gas chromatography-mass spectrometry and high-resolution two-dimensional electrophoresis is capable of mapping compounds of both low and high molecular mass. Used in combination with pattern-recognition analysis, the complete multicomponent analytical system opens the possibility of diagnosing diseased cells solely on the basis of differences in their biochemical composition.